PHARMACEUTICS DEPARTMENT FACULTY OF PHARMACY

MANSOURA UNIVERSITY

Prepared by:

Muhanad Soliman El-borolossy

HOW DO WE DEFINE CONSTIPATION? Unsatisfactory defecation characterized by infrequent stools, difficult stool passage, or both. Difficult stool passage includes straining, a sense of difficulty passing stool, incomplete evacuation, hard/lumpy stools, prolonged time to pass stool, or need for manual maneuvers to pass stool The ACG Chronic Constipation Task Force also clarified what is meant by chronic: Chronic constipation is defined as the presence of these symptoms for at least 3 months. Reduced frequency/ increased difficulty Leads to: Malaise,Anorexia,Abdominal discomfort,Colic Faecal incontinence-Nausea & Vomiting- Urinary retention-Psychological distress.

CAUSES OF CONSTIPATION Debility (Inactivity, inability to go to toilet at

right time)

Diet (poor oral intake of fluids or food esp. fibre)

Drugs (Opioids, Antiemetics, Anticholinergics, Diuretics)

Disordered Metabolism (Hypercalcaemia, Hypokalaemia, Hypothyroidism)

Disease (Cancer)

Disordered Neurology (eg Spinal Cord Compression, autonomic neuropatthy.

1. In most cases of chronic constipation, no specific cause is found (chronic idiopathic constipation)

2. Lifestyle Factors Inadequate fluid intake,Decreased food intake Inappropriate bowel habits< Immobility.

3. Medications

4. Endocrine and Metabolic disorders Hypothyroidism,Hypercalcemia, Hypokalemia,Pheochromocytoma.

5. Neurologic Parkinson's disease, Multiple sclerosis, Spinal lesions, Damage to sacral parasympathetic nerves,Autonomic neuropathy (Diabetes mellitus).

6. Psychological Depression Eating disorders (e.g., anorexia nervosa)

7. GI disorders: Irritable bowelsyndrome, Diverticulitis, Hemorrhoids and anal fissuresTumors, HerniaHirschsprung’s disease.

8. Pregnancy Natural increases in the hormones estrogen and progesterone, as well as increased pressure on a mother’s bowels from carrying the baby can both affect regularity in passing stools.

9. Age –because slowing of the bowel functions is a natural part of the aging process and because the elderly are often on medications that slow the gastrointestinal tract.

Constipation can also be the main symptom of a condition called irritable

bowel syndrome (IBS). IBS can be tough to diagnose because the symptoms

range and can shift over time. Some people with IBS experience

diarrhea,abdominal bloating, and/or cramps. Others mostly have

constipation.And some can alternate between these sets of symptoms. People

with IBS also often have recurrent or chronic abdominal pain.

Unfortunately, the cause of IBS is not well understood.

Some experts think the pain and discomfort of IBS may occur because the

gastrointestinal tract of patients with it are extra sensitive to stretch and

distention.Another theory is that the muscles and nerves work too quickly in

somepatients, causing diarrhea, or too slowly in other patients, causing

constipation.

Finally,

constipation is also

a common side

effect of many

medicines.

Morphine and other

“opioid-based”

painkillers(for

example,

oxycodone,codeine,

Vicodan, Percocet,

and Dilaudid) are the

worst offenders.

Most people who

take such medicines,

even over a short

period, will

experience

constipation.

Opioids cause constipation by slowing down bowel

function, leading to increased water absorption in the colon

and ultimately drier,harder stools that are difficult to pass.

Many other medicines are guilty, too. These include

certainantidepressants,cholesterol-lowering drugs, and over-the-counter

painkillers.

Taking Hæma-Caps® for anemia: Iron slows down the digestive system & slowing of normal bowel movement.This may be because iron is a metal in its basic form. Metals carry a charge that can affecting muscles and nerves in the bowel

Before starting treatment If you have constipation or occasionally suffer from it, the question of when to see a doctor is important.Most people with a transient bout of constipation don’t need to see a doctor, but you should if any of the following occur:

If your bowel movements have fallen to less than three per week for 2

weeks or longer.

If you have periodic and recurring episodes when you go 3 to 4 days

without a bowel movement

If you are “irregular” – say, with episodes of frequent bowel movements

followed by 3-4 days without one

If you often have feelings of abdominal bloating, cramping and

discomfort

If you have blood in your stools or it’s black or tarry-looking

If you experience pain when you have a bowel movement

If you have persistent or recurring abdominal pain

If there is a sudden and sharp change in how often you move your bowels

If you often have to strain during bowel movements and/or it takes a

long time to have one

If your stools are hard (rocky or pellet-like)

If your stools become very thin for more than a few days (a possible

indicator of colon cancer)

If you often have a sensation of incomplete evacuation after bowel

movements.

If over-the-counter treatments have failed to relieve your symptoms.

Before starting treatment Assess for faecal impaction and consider need for referral to exclude colon cancer in older patients with alarm symptoms or sudden change in bowel habit.Treat reversible causes, eg dehydration, depression, hypothyroidism, hypercalcaemia. The relationship between urinary incontinence and constipation can be complex: constipation may exacerbate urinary incontinence and treatment of urinary incontinence can lead to constipation, eg if fluid intake is decreased in an attempt to control urinary incontinence or if anticholinergic drugs are used. Assess for and manage urinary incontinence. Stop causative drugs if possible, eg aluminium antacids, opioids, drugs with anticholinergic effects, calcium or iron supplements, diuretics, verapamil. Ensure an accurate bowel chart is kept, recording time, amount and consistency of stool; this is useful for assessing when laxatives are required and response to treatment.

Two approaches to consider:

- Non-drug Approach -Drug Approach

Non-Drug Measures:

+ Increase calories in low calorie diets + Have a regular bowel regimen: patients should attempt to have a bowel movement at the same time each day especially after breakfast since colonic activity is highest at that time. Patients should not repress the urge to defecate or spend prolonged periods of time at the toilet. Placing a footstool in front of the toilet helps elevate the thighs, thus placing the pelvis in the optimum position for defecation. + Consume a high fibre diet: the target is 25-28g of fibre daily + Eat more fruits: apples, pears, and prunes contain the natural laxative sorbitol + Exercise: inactivity is associated with constipation + Weight loss: want BMI to be between 18.5-24.9

Inadequate dietary fibers

Diets include a good quantity of fibers are less likely to suffer from

constipation.

Fiber retains water, softening stool & ease evacuation.

Foods low in fiber : high fat food.

Foods rich in fiber: fruits, veg. and whole grain.

Normal daily fiber intake 10 ̴ 25 g.

Inadequate exercises

Walking help prevent constipation by promoting bowel motility.

Loss of defecatory reflex

If you ignore the urge to have a bowel movement.

The urge can gradually go away.

The longer can you delay it, the drier and harder stool will become.

Drug Approach

According to their mode of action.

1. Bulk-forming laxatives

2. Stimulant laxatives

3. Osmotic laxatives

4. Emollient laxatives (fecal softeners)

5. Lubricants

6. New Agents ex.(Lubiprostone)

Type of laxative Example(s) Approximate onset of action 1-Stimulant laxative Senna, Bisacodyl, and Glycerin(supp.) Oral:6-12hours Rectal: within 1 hour 2-Bulk-forming laxative Methylcellulose, Bran , and Ispaghula(Metamucil®) 1-3 days 3-Lubricant(faecal softeners) Liquid paraffin 6-8 hours 4-Osmotic laxative Lactulose 1-2 days

Natural: plant gum: agar, psyllium, and bran.

Synthetic: cellulose compounds methylcellulose and carboxy methylcellulose.

Onset of action: 8-24 hours

Peak action: 3 days

Benefits:

A bulk-forming laxative may help if you experience chronic constipation due to diet or medication. Some people prefer bulk-forming laxatives because there’s usually a more gradual improvement of constipation symptoms. They’re often the first line of defense before stimulant or other types of laxatives are used. There is also less risk of the cramping or explosive diarrhea that occurs with stimulant laxatives. Laxatives may be beneficial:

during pregnancy or for a few days after birth during surgery prep in treating constipation in bedridden people in treating constipation caused by medication in preventing strain after surgery in restoring normal bowel function after a period of poor eating or physical

inactivity in improving medical conditions made worse by straining, such as

hemorrhoids, heart disease, hernia, stroke, or high blood pressure

Bulk-forming laxatives may also be used to help reduce cholesterol or to treat diarrhea.

1- not absorbed from the intestines into the body safe for long-term use. 2- safe for elderly patients. 3- Helpful in patients with irritable bowel syndrome, diverticulosis, and colostomies. Should be mixed in a glass of water or juice, stirred and drunk

immediately followed by a half to a full glass of water.

Why with water or juice?

Because Insufficient fluid intake cause the drug to solidify in GI tract results in intestinal obstruction.

May not be appropriate for patients who must restrict oral fluid

intake (such as patients with kidney failure).

Patients with narrowing of the digestive tract (including esophageal

stricture, intestinal stricture, or severe adhesions)

--risk of blockage of the intestine or the esophagus.

Natural: plant gum: agar, psyllium, and bran.

1-Ispaghula + plantago seed + senna

(Agiolax®) 2 teaspoonfuls in wateronce or twice daily, preferably at mealtmes, child 1 teaspoonful ..

For diarrhea , 1teaspoonful 3 times daily. 2- Psyllium REGUMUCIL ® Powder Adult and children above 12 years take sachet 3 times daily.

2-Bran " Bran® "

- 1-2 capsule to be taken with ample of

water or fluids, 3 times daily. - 2-3 capsules daily during weight control

programs. 3-Plantago herb( laxiplant® ) granules Synthetic: cellulose compounds methylcellulose and carboxy methylcellulose. 1- Methylcellulose( bene fiber ) powder

2-Calcium polycarbophil (Evak®) (Evaculax®)tab 2 tabletes 1-4 times daily with sufficient of water

They can be used for acute or chronic (eg in neuromuscular disease) constipation contraindicated in intestinal obstruction, acute abdominal conditions and inflammatory bowel disease. They may cause abdominal discomfort and cramping increased risk of faecal inconti- nence in elderly patients -ensure adequate fluid intake with products that also contain a bulk-forming laxative (eg Normacol Plus®, Agiolax®) Administration: do not crush, chew or break EC tablets. Space milk, antacids, H2‐blockers & PPIs by 1 hour. Suppositories: insert 30 mins after a meal to align with gastrocolonic response.

CONTRAINDICATIONS abdominal pain with nausea &

vomiting, acute IBD, appendicitis,

ileus, galactose or fructose

intolerance, GI obstruction, severe

dehydration, tartrazine allergy.

ADVERSE

EVENTS

Oral: abdominal pain, cramps,

diarrhea, hypokalemia.

Suppository: rectal irritation or

burning.

Phenophthalein: Nausea, abdominal cramps, weakness, reddish brown urine) Bisacodyl: Fluid and electrolyte imbalance (Potassium and calcium) Mild cramping, and diarrhea

DRUG INTERACTIONS

Diuretics

‐ may risk of electrolyte disturbances.

EC tabs: milk, antacids, PPIs, or H2‐blockers

acidity causes early disintegration GI irritation.

Chronic, long-term use of stimulant laxatives can lead to: loss of colon function (cathartic colon). Consequently, constipation becomes increasingly worse and unresponsive to laxatives.

2. Cascara and Senna

It is used to treat constipation and also to clear the bowel before diagnostic tests

such as colonoscopy.

Senna is also used for irritable bowel syndrome (IBS), hemorrhoids, and weight

loss.patient shouldn't use senna if they experience abdominal pain or diarrhea.

How does it work?

Senna contains many chemicals called sennosides. Sennosides irritate the lining of the

bowel, which causes a laxative effect.

uses

in case of Constipation. Taking senna by mouth is effective for short-term treatment of constipation. Senna is an FDA-approved nonprescription drug for adults and children ages 2 years and older. However, in children ages 3-15 years, mineral oil and a medication called lactulose might be more effective than taking senna. Senna also appears to be effective for treating constipation when used in combination with psyllium or docusate sodium. In elderly people, senna plus psyllium is more effective than lactulose for treating ongoing constipation. Senna plus docusate sodium is effective for treating constipation in the elderly and in people who have undergone anorectal surgery. Taking senna appears to be as effective as lactulose, psyllium, and docusate for relieving constipation in people taking opioids or loperamide.

Side effects: Senna is LIKELY SAFE for most adults and children over age 2

when taken by mouth, short-term. Senna is POSSIBLY UNSAFE when taken by mouth long-term or in high doses. Don't use senna for more than two weeks. Longer use can cause the bowels to stop functioning normally and might cause dependence on laxatives. Electrolyte disturbances, potassium deficiency: Overuse of senna can make these conditions worse.

Dehydration, diarrhea or loose stools: Senna should not be used in people with dehydration, diarrhea, or loose stools. It can make these conditions worse.

Gastrointestinal (GI) conditions: Senna should not be used by people with abdominal pain (either diagnosed or undiagnosed), intestinal blockage, Crohn's disease, ulcerative colitis, appendicitis, stomach inflammation, anal prolapse, or hemorrhoids.

Heart disease: Senna can cause electrolyte disturbances and might make heart disease worse.

Interactions: Digoxin (Lanoxin) interacts with SENNA Senna is a type of laxative called a stimulant laxative. Stimulant laxatives can decrease potassium levels in the body. Low potassium levels can increase the risk of side effects of digoxin (Lanoxin).

Warfarin (Coumadin) interacts with SENNA Senna can work as a laxative. In some people senna can cause diarrhea. Diarrhea can increase the effects of warfarin and increase the risk of bleeding. If you take warfarin do not to take excessive amounts of senna.

Dose: BY MOUTH:

Senna is an FDA-approved nonprescription drug. For constipation in adults and children age 12 and over: the usual dose is 17.2 mg daily. Don't take more than 34.4 mg per day. For constipation in children: 8.5 mg daily increased just enough to cause one bowel movement daily has been used. For constipation in elderly people: 17 mg daily has been used. For constipation following pregnancy: 28 mg in 2 divided doses has been used.

ascara is a shrub. The dried bark is used to make medicine.

Cascara Cascara is used as a laxative for constipation, as well as a treatment for gallstones, liver ailments, and cancer. Some people use it as a “bitter tonic.” How does it work? Cascara contains chemicals that stimulate the bowel and have a laxative effect. side effects: Cascara is POSSIBLY SAFE for most adults when taken by mouth for less than one week. Side effects include stomach discomfort and cramps. Cascara is POSSIBLY UNSAFE when used long-term. Don’t use cascara for longer than one or two weeks. Long-term use can cause more serious side effects including dehydration; low levels of potassium, sodium, chloride, and other “electrolytes” in the blood; heart problems; muscle weakness; and others. Special Precautions & Warnings: Pregnancy and breast-feeding: Not enough is known about the use of cascara during pregnancy. Stay on the safe side and avoid use if you are pregnant. Cascara is POSSIBLY UNSAFE when taken by mouth while breast-feeding. Cascara can cross into breast milk and might cause diarrhea in a nursing infant. Children: Cascara is POSSIBLY UNSAFE in children when taken by mouth. Don’t give cascara to children. They are more likely than adults to become dehydrated and also harmed by the loss of electrolytes, especially potassium. Gastrointestinal (GI) disorders such as intestinal obstruction, Crohn’s disease, ulcerative colitis, appendicitis, stomach ulcers, or unexplained stomach pain interactions: Digoxin (Lanoxin) interacts with CASCARA Cascara is a type of laxative called a stimulant laxative. Stimulant laxatives can decrease potassium levels in the body. Low potassium levels can increase the risk of side effects of digoxin (Lanoxin). Medications taken by mouth (Oral drugs) interacts with CASCARA Cascara is a laxative. Laxatives can decrease how much medicine your body absorbs. Decreasing how much medicine your body absorbs can decrease the effectiveness of your medication. Stimulant laxatives interacts with CASCARA Cascara is a type of laxative called a stimulant laxative. Stimulant laxatives speed up the bowels. Taking cascara along with other stimulant laxatives could speed up the bowels too much and cause dehydration and low minerals in the body. Some stimulant laxatives include bisacodyl (Correctol, Dulcolax), castor oil (Purge), senna (Senokot), and others. Warfarin (Coumadin) interacts with CASCARA Cascara can work as a laxative. In some people cascara can cause diarrhea.

Diarrhea can increase the effects of warfarin and increase the risk of bleeding. If you take warfarin do not to take excessive amounts of cascara.

dose: BY MOUTH: As a laxative for constipation: 20-30 mg per day of the active ingredient (hydroxyanthracene derivatives). A typical dose is 1 cup of tea, which is made by steeping 2 grams of finely chopped bark in 150 mL of boiling water for 5-10 minutes, and then straining. The cascara liquid extract is taken in a dose of 2-5 mL three times daily. The appropriate amount of cascara is the smallest dose that is needed to maintain soft stools.

castor oil:

Uses Castor oil is used to treat constipation. It may also be used to clean out the intestines before a bowel examination/surgery. Castor oil is known as a stimulant laxative. It works by increasing the movement of the intestines, helping the stool to come out. How to use castor oil Take this medication on an empty stomach. Measure the dose carefully using a special measuring device/cup. Do not use a household spoon because you may not get the correct dose. You may take this medication with juice to improve the taste... t may take 6 to 12 hours before this medication causes a bowel movement. Tell your doctor if your condition persists or worsens, or if bleeding from the rectum occurs. If you think you may have a serious medical problem, seek immediate medical attention. Side Effects Stomach/abdominal pain or cramping, nausea, diarrhea, or weakness may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly. A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing. Precautions Before taking castor oil, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details. Before using this medication, tell your doctor or pharmacist your medical history, especially of: appendicitis or symptoms of appendicitis (such as nausea/vomiting, sudden or unexplained stomach/abdominal pain), a sudden change in bowel habits that lasts for longer than 2 weeks, bleeding from the rectum, intestinal blockage. It is unknown if this medication passes into breast milk. Consult your doctor before breast-feeding. Symptoms of overdose may include: severe stomach/abdominal pain or cramping, persistent nausea/vomiting/diarrhea.

Milk of Magnesia Considered a saline laxative, Milk of Magnesia is available over the counter. This product is rarely recommended by physicians in the modern era because safer and more effective alternatives exist. Milk of Magnesia should be avoided by anyone who suffers from heart or kidney disease Dose: Children: 1‐3mL/kg/day of 400mg/5mL Adults: 2400‐4800mg po HS or divided up to TID (e.g. 30‐60mL of the 400mg/5mL strength)

sorbitol

(Sorbilax®) Lactulose

( Duphalac®)

1–3 days

use in opioid-induced constipation contraindicated in intestinal obstruction not suitable for acute relief of constipation due to slow onset of effect flatulence is common

Lactulose, g

667mg/mL oral soln

( portal systemic encephalopathy)

Onset of Action: 24‐48 hours

Administration: sweetness can be unpalatable. Mask taste by diluting in water, fruit juice, milk or desserts. Certain brands may be more palatable.

CONTRAINDICATIONS: galactose free diet

Side effects: transient, dose‐dependent abdominal cramps, flatulence, nausea, diarrhea.

DRUG INTERACTIONS antacids (lactulose decrease colonic pH). May interact with anti‐infectives (decrease the colonic bacteria that degrade lactulose) & warfarin (increase INR due decrease intestinal absorption of vitamin K).

Dose <1yr: 1‐3mL/kg/day divided BID 1‐5yrs: 5mL po BID 6‐12yrs: 10mL po BID Adults & >12yrs: 15‐30mL po daily up to TID. Max 90mL/day for constipation.

Sorbitol 70% solution, g

Onset of Action:

PO: 24‐48 hours

PR: 5‐15 minutes

Less sweet than lactulose, less nausea

CONTRAINDICATIONS: severe cardiopulmonary or renal impairment

Side effects: abdominal cramping, bloating, flatulence

DRUG INTERACTIONS sodium polystyrene sulfonate ( risk of intestinal necrosis)

Dose Children: 1‐3mL/kg/day 70% soln po daily‐BID, 30‐60mL pr as 25‐50% soln (dilute 70% soln with water)

Adults: 15‐30mL 70% soln po daily‐BID, 120mL pr as 25‐30% soln (dilute 70% soln with water)

MiralaxMiralax (polyethylene glycol PEG) is a medication that draws

water into the stool, resulting in a softer stool and inducing more frequent bowel movements. No need for a prescription, Miralax is available over the counter. There is one published report that Miralax was more effective than Zelnorm in increasing the number of bowel movements and improving symptoms in patients who suffer from chronic constipation. Miralax seems to cause fewer gastrointestinal side effects (such as bloating and flatulence) than the other osmotic laxatives

4-. GlycerinSuppositories: Adult 2.65g/supp Infant/Child: 1.8g/supp Onset of Action: 15‐60 minutes Less effective if stool is dry & hard. CONTRAINDICATIONS: anal fissures, fistula, hemorrhoids, proctitis SIDE EFFECTS : rectal irritation DRUG INTERACTION : no known significant DIs DOSE: 2yrs: ½ infant/child supp daily pr PRN (split lengthwise) 3‐5yrs: 1 infant/child supp daily pr PRN Adult & ≥6yrs: 1 adult supp daily pr PRN

Docusate Sodium COLACE,capsule: 100, 200, 250mg drops: 10mg/mL syrup: 4, 20, 50mg/mL Combination Product: SENOKOT‐S, g tablet(docusate Na+50mg +sennosides 8.6mg) Onset of Action: 12‐72 hours Use: May help to prevent constipation or straining if recent rectal surgery or myocardial infarction, anorectal disorders, postpartum & unstable angina. Administration: syrup & drops taste bitter; mask by diluting in 120mL of milk, fruit juice or infant formula. ENEMAS (use drops, 10mg/mL): Retention: 5‐90mL daily pr PRN Flushing: 1‐100mL daily pr PRN Dose: <3yrs: 10‐40mg po daily or BID 3‐6yrs: 20‐60mg po daily or BID 6‐12yrs: 40‐150mg po daily or BID Adults & >12yrs: 100mg po BID CONTRAINDICATIONS: acute abdominal pain, nausea, vomiting ADVERSE EVENTS: well tolerated; occasional mild, transient nausea, GI cramping or rash. Throat irritation with docusate sodium solutions. DRUG INTERACTIONS mineral oil ( absorption of mineral oil),ASA ( risk of mucosal damage). Theoretically may absorption of other medications; may space narrow therapeutic agents by 2 hours.

Mineral Oil (Heavy USP) enema FLEET MINERAL OIL, g oral liquid Combination Products: MAGNOLAX oral liquid (each mL = 0.25mL mineral oil + 60mg magnesium hydroxide) Onset of Action: PO: 6‐8 hours PR: 2‐15 minutes Administration: to compliance esp. with peds mix with fruit juice or carbonated beverages, & chill to viscosity. Not recommended for chronic use. CI: infants, bedridden or dysphagic pts risk of aspiration;appendicitis; undiagnosed rectal bleeding. AE: lipid pneumonia, perianal pruritus if incontinent DI: docusate ( absorption of mineral oil), may absorption of oral contraceptives, digoxin & possibly fat soluble vitamins A, D, E, & K, may anticoagulant effect due to vitamin K. Dose: 6‐12yrs: 10‐25mL po HS while sitting up. Disimpaction: 15‐30mL/year of age orally (max 240mL) Adults & >12yrs: 15‐45mL po HS while sitting up ENEMA 2‐12yrs: 30‐60mL daily pr PRN Adults & 12yrs: 60‐150mL OD pr PRN, usual dose: 120mL

6- New Agents LUBIPROSTONE

Amitiza GENERIC NAME(S): LUBIPROSTONE

Dosage Form: capsule, gelatin coated

Mechanism of action: Opening of chloride channels locally in the GI luminal epithelium, which stimulates chloride-rich intestinal fluid secretion and shortens GI transit time

Indications and Usage for Amitiza

Chronic Idiopathic Constipation

Amitiza® is indicated for the treatment of chronic idiopathic constipation in

adults.

Opioid-induced Constipation

Amitiza is indicated for the treatment of opioid-induced constipation (OIC) in

adults with chronic non-cancer pain.

Limitations of Use:

Effectiveness of Amitiza in the treatment of opioid-induced constipation in patients taking diphenylheptaneopioids (e.g., methadone) has not been established.

Irritable Bowel Syndrome with Constipation

Amitiza is indicated for the treatment of irritable bowel syndrome with

constipation (IBS-C) in women ≥ 18 years old.

Amitiza Dosage and Administration

Chronic Idiopathic Constipation and Opioid-induced Constipation

The recommended dose is 24 mcg twice daily orally with food and water.

Dosage in patients with hepatic impairment

For patients with moderately impaired hepatic function (Child-Pugh Class B), the

recommended starting dose is 16 mcg twice daily. For patients with severely

impaired hepatic function (Child-Pugh Class C), the recommended starting dose

is 8 mcg twice daily. If this dose is tolerated and an adequate response has not

been obtained after an appropriate interval, doses can then be escalated to full

dosing with appropriate monitoring of patient response [see Use in Specific

Populations and Clinical Pharmacology ].

Irritable Bowel Syndrome with Constipation

The recommended dose is 8 mcg twice daily orally with food and water.

Dosage Forms and Strengths

Amitiza is available as an oval, gelatin capsule containing 8 mcg or 24 mcg of lubiprostone. •8 mcg capsules are pink and are printed with "SPI" on one side

•24 mcg capsules are orange and are printed with "SPI" on one side

Side Effects Nausea, diarrhea, gas, vomiting, dry mouth, runny nose, cough, fever, headache, joint/back pain, or trouble sleeping may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly. Lubiprostone may rarely cause trouble breathing and chest tightness within 30 to 60 minutes after the first dose. This reaction is usually not serious and generally goes away within 3 hours. It may happen again with other doses. However, you may not be able to tell this reaction apart from a rare, severe reaction that also causes trouble breathing and/or chest pain. Symptoms of a serious allergic reaction may include: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing. Precautions Before using this medication, tell your doctor or pharmacist your medical history, especially of: certain stomach/intestinal problems (blockage, severe diarrhea), liver disease. During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor. It is unknown if this drug passes into breast milk, but it may have undesirable effects (such as causing diarrhea) on a nursing infant.

Summary

Indications

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